The proposed research is designed to study the genetics, immunology and cellular basis of the Hemopoietic-histocompatibility (Hh) system, that is, the H-2 linked genetic controls of tissue-specific Hh alloantigens selectively expressed on hemopoietic cells; immune responsiveness or suppression to such antigens; and the role of Hh genesis associated with subregions of the major histocompatibility complex in resistance to bone marrow allografts, orderly stem cell proliferation and differentiation (hemopoiesis), and immune surveillance over leukemogenesis. The primary goal is to test the hypothesis that Hh gene products are a new class of polymorphic cell-surface differentiation antigens recognizable by syngeneic as well as allogeneic cells of the immune system. Experiments will be performed in vivo (bioassays for resistance to graft proliferation) and in vitro (induction of cell mediated immunity against Hh-bearing target cells) and designed so as to detect and quantitate variations of Hh-gene expression in stimulating and target cells, and variations of immunocompetence in responder animals or cells. Antisera specific for restricted subregions of the major histocompatibility complex (to which Hh genes are linked) will be produced in multiple donor-recipient combinations and the sera will be used for the detection of Hh molecules on cells and for isolation and purification attempts. Responder, effector and stimulator cells will also be defined by cell-surface markers such as Ly and Ia alloantigens and antisera of restricted specificity (e.g., anti-Ia, anti-H-2D, etc.) will be tested for the ability to prevent stimulation or effector:target cell interaction. The dependence on macrophages and lymphocyte subpopulations of anti-Hh reactions will be studied both in vivo and in vitro with selective antimacrophage (silica particles, carrageenans) and antilymphocyte (specific antisera) agents, and with anti-species sera which according to preliminary results are suppressive for anti-Hh but not for other immune responses. Genetically defined mouse and human cells will be used for the in vitro experiments.